Recent Advances in Microfluidic Techniques for Systems Biology

Sun, Gongchen; Lu, Hang

doi:10.1021/acs.analchem.8b04757

Cited by 10 publications

(5 citation statements)

References 114 publications

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“…This approach can however be effective for experiments with low cell numbers, as cells can be directly picked from complex multicellular microenvironments. Isolated culture approaches in contrast can be scaled to 10's or 1,000's of individual cells using microfluidic technology [225], but an inherent limitation is that cells will not receive the cell-cell contacts and soluble factors from other cells in their microenvironment. In one isolation culture approach, researchers used an ECM coated Fluidigm C1 chip to isolate individual cells into microwells then applied fluorescence microscopy to track NF-kB transcription factor reporter activity over time after lipopolysaccharide stimulation [226].…”

Section: Spatially Resolved Omics Within Engineered Microsystemsmentioning

confidence: 99%

“…The most conceptually straightforward approach to link single cell microenvironment-driven function to a systems-level molecular phenotype is to isolate and index individual cells from culture after observing their behavior and function. Single cell isolation (165,166) can be achieved by physically picking cells using a micromanipulation system, with microfluidic systems (167), or by culturing cells in isolation in microwells. However, current systems for cell picking by micromanipulation remain low throughput and labor intensive to operate (155,165,166).…”

Section: Spatially Resolved Omics Within Engineered Microsystemsmentioning

confidence: 99%

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Towards systems tissue engineering: Elucidating the dynamics, spatial coordination, and individual cells driving emergent behaviors

2020

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Biomaterial systems have enabled the in vitro production of complex, emergent tissue behaviors that were not possible with conventional two-dimensional culture systems, allowing for analysis of both normal development and disease processes. We propose that the path towards developing the design parameters for biomaterial systems lies with identifying the molecular drivers of emergent behavior through leveraging technological advances in systems biology, including single cell omics, genetic engineering, and high content imaging. This growing research opportunity at the intersection of the fields of tissue engineering and systems biology -systems tissue engineeringcan uniquely interrogate the mechanisms by which complex tissue behaviors emerge with the potential to capture the contribution of i) dynamic regulation of tissue development and dysregulation, ii) single cell heterogeneity and the function of rare cell types, and iii) the spatial distribution and structure of individual cells and cell types within a tissue. By leveraging advances in both biological and materials data science, systems tissue engineering can facilitate the identification of biomaterial design parameters that will accelerate basic science discovery and translation.

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Section: Spatially Resolved Omics Within Engineered Microsystemsmentioning

confidence: 99%

Section: Spatially Resolved Omics Within Engineered Microsystemsmentioning

confidence: 99%

Towards systems tissue engineering: Elucidating the dynamics, spatial coordination, and individual cells driving emergent behaviors

2020

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“…Many research works have demonstrated its advantages in having fast isolation speed and high efficiency of data acquisition. It is capable of integrating multiple workflows that enables parallelization and streamlining of complex protocols, which allows automation and control of analytical functions, cell and cell environment manipulation, and simultaneous detection and quantification of secreted molecules 3,4 . For instance, conventional approaches don't take into account the phenotypic and functional state of heterogenous cells which microfluidics technology is able to address.…”

Section: Introductionmentioning

confidence: 99%

Design and Optimizations of a High-throughput Valve-based Microfluidic Device for Single Cell Compartmentalization and Analysis

Briones

Espulgar

Koyama

et al. 2020

Preprint

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The need for high throughput single cell screening platforms has been increasing with advancements in genomics and proteomics to identify heterogeneity, unique cell subsets or super mutants from thousands of cells within a population. For real-time monitoring of enzyme kinetics and protein expression profiling, valve-based microfluidics or pneumatic valving that can compartmentalize single cells is advantageous by providing on-demand fluid exchange capability for several steps in assay protocol and on-chip culturing. However, this technique is throughput limited by the number of compartments in the array. Thus, one big challenge lies in increasing the number of microvalves to several thousand that can be actuated in the microfluidic device to confine enzymes and substrates in picoliter volumes. This work explores the design and optimizations done on a microfluidic platform to achieve high-throughput single cell compartmentalization as applied to single-cell enzymatic assay for protein expression quantification. Design modeling through COMSOL Multiphysics was utilized to determine the circular microvalve’s optimized parameters, which can close thousands of microchambers in an array at lower sealing pressure. Multiphysical modeling results demonstrated the relationships of geometry, valve dimensions, and sealing pressure, which were applied in the fabrication of a microfluidic device comprising of up to 5000 hydrodynamic traps and corresponding microvalves. Comparing the effects of geometry, actuation media and fabrication technique, a sealing pressure as low as 0.04 MPa was achieved. Applying to single cell enzymatic assay, variations in granzyme B activity in Jurkat and human PBMC cells were observed. Improvement in the microfluidic chip’s throughput is significant in single cell analysis applications, especially in drug discovery and treatment personalization.

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“…Droplet microfluidics is an interdisciplinary field and has received worldwide attention due to its remarkable features of a minute volume of reagents, high surface-to-volume ratio, avoidance of cross contamination, excellent flexibility, and integrability. − Moreover, multiple discrete droplets can be implemented to function as an independent microreactor, allowing for in-parallel manipulation and thereby high throughput. Tremendous progress has been achieved in both fundamental techniques and industrial applications in chemistry, biology, medicine, and environment . Upon stimuli (such as surface wetting gradient, electrical field, electromagnetic field, or light, etc.…”

mentioning

confidence: 99%

“…1−3 Moreover, multiple discrete droplets can be implemented to function as an independent microreactor, allowing for in-parallel manipulation and thereby high throughput. Tremendous progress has been achieved in both fundamental techniques 4 and industrial applications in chemistry, 5 biology, 6 medicine, 7 and environment. 8 Upon stimuli (such as surface wetting gradient, 9 electrical field, 10 electromagnetic field, 11 or light, 12 etc.…”

mentioning

confidence: 99%

Light Controlled 3D Crystal Morphology for Droplet Evaporative Crystallization on Photosensitive Hydrophobic Substrate

Chen

Zhu

et al. 2022

J. Phys. Chem. Lett.

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Controlling crystal morphology is crucial in analytical chemistry and smart materials synthesis, etc. However, flexible manipulation of 3D crystal morphology still remains challenging. Herein, we present a novel and facile light strategy for droplet evaporative crystallization to manipulate macroscopic crystal morphology on photosensitive hydrophobic substrate possessing photothermal conversion property. We demonstrate that the spherical coronal shell and alms bowl-like crystal skeletons can be achieved on smooth photosensitive hydrophobic substrate, depending on the salt concentration. Rough photosensitive hydrophobic substrate further creates a bubble-assisted light strategy, by which a cylindrical shell-like crystal skeleton with a directionally controllable cavity is achieved. Amazingly, the proper additive endows droplet evaporative crystallization to form a closed crystal skeleton with the solution wrapped inside. The present study provides new ideas for designing a novel optical droplet microfluidic platform for controlling crystal morphology.

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Recent Advances in Microfluidic Techniques for Systems Biology

Cited by 10 publications

References 114 publications

Towards systems tissue engineering: Elucidating the dynamics, spatial coordination, and individual cells driving emergent behaviors

Towards systems tissue engineering: Elucidating the dynamics, spatial coordination, and individual cells driving emergent behaviors

Design and Optimizations of a High-throughput Valve-based Microfluidic Device for Single Cell Compartmentalization and Analysis

Light Controlled 3D Crystal Morphology for Droplet Evaporative Crystallization on Photosensitive Hydrophobic Substrate

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